EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Molecular basis for Gβγ-mediated activation of phosphoinositide 3-kinase γ.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 31, Issue 8, Page 1198-1207, Year 2024
掲載日	2024年4月2日
著者	Chun-Liang Chen / Ramizah Syahirah / Sandeep K Ravala / Yu-Chen Yen / Thomas Klose / Qing Deng / John J G Tesmer /
PubMed 要旨	The conversion of phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-triphosphate by phosphoinositide 3-kinase γ (PI3Kγ) is critical for neutrophil chemotaxis and cancer metastasis. ...The conversion of phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-triphosphate by phosphoinositide 3-kinase γ (PI3Kγ) is critical for neutrophil chemotaxis and cancer metastasis. PI3Kγ is activated by Gβγ heterodimers released from G protein-coupled receptors responding to extracellular signals. Here we determined cryo-electron microscopy structures of Sus scrofa PI3Kγ-human Gβγ complexes in the presence of substrates/analogs, revealing two Gβγ binding sites: one on the p110γ helical domain and another on the p101 C-terminal domain. Comparison with PI3Kγ alone reveals conformational changes in the kinase domain upon Gβγ binding that are similar to Ras·GTP-induced changes. Assays of variants perturbing the Gβγ binding sites and interdomain contacts altered by Gβγ binding suggest that Gβγ recruits the enzyme to membranes and allosterically regulates activity via both sites. Studies of zebrafish neutrophil migration align with these findings, paving the way for in-depth investigation of Gβγ-mediated activation mechanisms in this enzyme family and drug development for PI3Kγ.
リンク	Nat Struct Mol Biol / PubMed:38565696 / PubMed Central
手法	EM (単粒子)
解像度	3.03 - 3.9 Å
構造データ	40650 8so9 EMDB-40650, PDB-8so9: Phosphoinositide phosphate 3 kinase gamma 手法: EM (単粒子) / 解像度: 3.03 Å 40651 8soa EMDB-40651, PDB-8soa: Phosphoinositide phosphate 3 kinase gamma bound with ATP 手法: EM (単粒子) / 解像度: 3.32 Å 40652 8sob EMDB-40652, PDB-8sob: Phosphoinositide phosphate 3 kinase gamma bound with ADP 手法: EM (単粒子) / 解像度: 3.9 Å 40653 8soc EMDB-40653, PDB-8soc: Phosphoinositide phosphate 3 kinase gamma bound with ADP and Gbetagamma 手法: EM (単粒子) / 解像度: 3.5 Å 40654 8sod EMDB-40654, PDB-8sod: Phosphoinositide phosphate 3 kinase gamma bound with ADP and two Gbetagamma subunits in State 1 手法: EM (単粒子) / 解像度: 3.4 Å 40655 8soe EMDB-40655, PDB-8soe: Phosphoinositide phosphate 3 kinase gamma bound with ADP and two Gbetagamma subunits in State 2 手法: EM (単粒子) / 解像度: 3.6 Å
化合物	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM
由来	sus scrofa (ブタ) bos taurus (ウシ)
キーワード	SIGNALING PROTEIN / Phosphoinositide 3-Kinase / Chemotaxis / Cancer